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Biomedical subjects

Daisuke Shimizu

Publications and source records attributed to Daisuke Shimizu.

30 records · Page 2Linked to original sources

Survivin, a potential biomarker in the development of Barrett's adenocarcinoma.

BACKGROUND: Survivin, a member of the inhibitor-of-apoptosis family, is reported to be overexpressed in esophageal cancer but no data are available about its status in the metaplastic/dysplastic sequence. The aim of this study was to measure survivin gene expression in normal squamous/columnar epithelium and in the various stages of development of Barrett's adenocarcinoma. METHODS: Endoscopic biopsy or operative specimen samples from 5 tissue types were analyzed: (1) squamous epithelium from 3 cm above the gastroesophageal junction in patients with a negative pH study and no histologic injury (n = 17, pH- control); (2) antral tissue from patients with no evidence of Barrett's, dysplasia, or cancer (n = 29, antral control); (3) specialized intestinal metaplasia from patients with Barrett's esophagus (n = 16; Barrett's group); (4) low- or high-grade dysplasia (n = 12, dysplasia group), and (5) adenocarcinoma (n = 45 cancer group). After laser-capture microdissection cellular RNA was extracted from each tissue and reverse transcribed to complementary DNA. Expression levels of survivin were measured by reverse-transcription polymerase chain reaction. RESULTS: Survivin gene expression was greater in columnar (antral) compared with squamous (pH-) control tissues (P = .03). Expression in quiescent Barrett's epithelium was similar to both control tissues. Expression levels in dysplastic epithelium were greater than in squamous control (P = .01) and Barrett's tissues (P = .04), but not higher than columnar control tissues, whereas expression in adenocarcinoma was greater than all tissues except dysplasia (P < .001). CONCLUSIONS: Survivin expression may be a biomarker in the development of Barrett's adenocarcinoma that is able to distinguish between quiescent Barrett's, dysplastic Barrett's, and Barrett's adenocarcinoma.

Adenocarcinoma↗

Thrombocytopenia due to cytomegalovirus infection in an immunocompetent adult.

A healthy 33-year-old man presented with a short history of viral infection and recent petechiae. Examination of the blood showed a profound thrombocytopenia. He was diagnosed as having cytomegalovirus infection by serological examination. A high level of platelet-associated immunoglobulins was demonstrated suggesting an immune basis for the thrombocytopenia and we, therefore, treated the patient with bolus methylprednisolone and gamma-globulin, resulting in prompt recovery. Recognition for CMV-induced thrombocytopenia is important for early diagnosis.

Adult↗

Scrotal Ulcers Arising during Treatment with All-trans Retinoic Acid for Acute Promyelocytic Leukemia.

All-trans retinoic acid (ATRA) is effective in approximately 90% of the cases of acute promyelocytic leukemia (APL) with a low incidence of adverse effects. We report a patient with APL who developed skin ulcers of the scrotum concomitant with high fever during treatment that included ATRA. Severe fever was promptly alleviated with discontinuation of ATRA, while the ulcers improved gradually over 3 months. As the clinical features are similar to those of Sweet's syndrome, we should be aware of the possibility that this rare adverse effect may occur in the treatment with ATRA.

Adult↗

Prediction of chemosensitivity of colorectal cancer to 5-fluorouracil by gene expression profiling with cDNA microarrays.

5-Fluorouracil (5-FU) is the most widely used anticancer agent for gastrointestinal cancers. Because many tumors show primary resistance, it is clinically meaningful to predict tumor sensitivity to the drug before treatment. cDNA microarrays containing 21,168 clones were used to identify genes associated with sensitivity to 5-FU. Gene expression profiling of 3 colorectal cancer cell lines (DLD-1, HT-29 and NUGC-3) and the corresponding 5-FU-resistant sublines (DLD-1/FU, HT-29/FU and NUGC-3/5FU/L) showed 81 genes that were differentially expressed. The gene set thus identified successfully predicted the sensitivities of 5 other colorectal cancer cell lines and could also separate 5-FU resistant clinical samples from sensitive ones.

Antimetabolites, Antineoplastic↗

Hepatitis B virus reactivation in a patient undergoing steroid-free chemotherapy.

A 62-year-old Japanese man who was positive for hepatitis B surface antigen (HBsAg) and anti-HBe antibody, underwent chemotherapy for non-Hodgkin's lymphoma (NHL). Mutations were detected in the precore region (nt1896) of HBV. Because steroid-containing regimen may cause reactivation of hepatitis B virus (HBV) and hepatitis may progress to be fulminant after its withdrawal, we administered CHO (CPA, DOX and VCR) therapy and the patient obtained complete response. However, he developed acute exacerbation of hepatitis due to HBV reactivation. Recovery was achieved with lamivudine (100 mg/d) and plasma exchange. The present case suggests that acute exacerbation of hepatitis can occur with steroid-free regimen. Because the efficacy of the prophylactic use of lamivudine has been reported and the steroid enhances curability of malignant lymphoma, the steroid containing regimen with prophylaxis of lamivudine should be evaluated further.

Antineoplastic Combined Chemotherapy Protocols↗

Preliminary analysis of Nacholapithecus scapula and clavicle from Nachola, Kenya.

The Miocene ape Nacholapithecus is known from rather complete skeletons; some of them preserve the shoulder joint, identified by three scapulae and one clavicle. Comparisons made with other Miocene and living apes ( Proconsul, Equatorius, Ugandapithecus) suggest that the mobility of the scapulohumeral joint was important, and scapular features such as the morphology and position of the spine and the morphology of the acromion and axillary border resemble those of climbing arboreal primates except for chimpanzees, gorillas, or orang-utans. From the size of the scapula (male Nasalis size), it is clear that the animal is smaller than an adult chimpanzee, but the clavicle is almost as relatively long as those of chimpanzees. Some features closer to colobine morphology reinforce the hypothesis that Nacholapithecus was probably a good climber and was definitely adapted for an arboreal life.

Animals↗

Current progress in the prediction of chemosensitivity for breast cancer.

Advances in chemotherapy have improved the prognosis of patients with breast cancer significantly. Individualization is important for optimization of chemotherapy. The prediction of tumor sensitivity to anticancer agents has been intensively investigated for that purpose. There have been 2 approaches to predict the efficacy of drugs against individual tumors, drug-sensitivity tests and molecular marker genes. Although some of these tests are already available clinically, the prediction of chemosensitivity remains a goal to be achieved. Several studies with microarrays revealed that comprehensive analyses of genes may provide useful information for determining the chemosensitivity of cancer. We have started to use a cDNA microarray to study the chemosensitivity of breast cancer. Taken together with recent data, studies for drug sensitivity should provide insights into the mechanisms of drug sensitivity and the optimal design of more effective treatment strategies in breast cancer.

Adult↗

Quantitative, tissue-specific analysis of cyclooxygenase gene expression in the pathogenesis of Barrett's adenocarcinoma.

Cyclooxygenase (Cox-2) is implicated in the pathogenesis of many cancers including esophageal adenocarcinoma (EAC), whereas the role of the isoform Cox-1 in carcinogenesis is not well understood. To further elucidate the role of these factors in the development of EAC, we measured the gene expressions (mRNA levels) of Cox-2 and Cox-1 by real-time quantitative polymerase chain reaction (QRT-PCR) in tissues from normal esophagus with and without erosive gastroesophageal reflux disease (GERD), Barrett's esophagus (BE), dysplasia, adenocarcinoma, and in healthy gastric antrum. All tissues were purified by laser capture microdissection from endoscopic or surgical resection specimens. Median Cox-2 gene expression did not differ significantly among the esophageal control groups but was elevated 5-fold in BE, 8-fold in dysplasia and 16-fold in EAC compared to normal esophageal controls with no erosive GERD. Erosive GERD tissue had slightly higher median Cox-2 expression but Cox-2 expression in normal antrum was much higher than that in a normal esophagus, close to that of dysplasia. In contrast to that of Cox-2, Cox-1 expression was significantly decreased in all neoplastic tissues compared to normal controls. Cox-1 and Cox-2 expression varied over a wide range in the neoplastic tissues but over a relatively narrow range in the esophageal normal tissues. The occurrence of substantial alterations in Cox-1 and Cox-2 expression at the BE stage indicates that these are early events in the development of EAC. These results confirm the important role of Cox-2 amplification in the pathogenesis of esophageal adenocarcinoma, but the unexpected down-regulation of Cox-1 raises questions about its role in carcinogenesis.

Adenocarcinoma↗

Systematic expression profiling of the mouse transcriptome using RIKEN cDNA microarrays.

The number of known mRNA transcripts in the mouse has been greatly expanded by the RIKEN Mouse Gene Encyclopedia project. Validation of their reproducible expression in a tissue is an important contribution to the study of functional genomics. In this report, we determine the expression profile of 57,931 clones on 20 mouse tissues using cDNA microarrays. Of these 57,931 clones, 22,928 clones correspond to the FANTOM2 clone set. The set represents 20,234 transcriptional units (TUs) out of 33,409 TUs in the FANTOM2 set. We identified 7206 separate clones that satisfied stringent criteria for tissue-specific expression. Gene Ontology terms were assigned for these 7206 clones, and the proportion of 'molecular function' ontology for each tissue-specific clone was examined. These data will provide insights into the function of each tissue. Tissue-specific gene expression profiles obtained using our cDNA microarrays were also compared with the data extracted from the GNF Expression Atlas based on Affymetrix microarrays. One major outcome of the RIKEN transcriptome analysis is the identification of numerous nonprotein-coding mRNAs. The expression profile was also used to obtain evidence of expression for putative noncoding RNAs. In addition, 1926 clones (70%) of 2768 clones that were categorized as "unknown EST," and 1969 (58%) clones of 3388 clones that were categorized as "unclassifiable" were also shown to be reproducibly expressed.

Animals↗

Functional implications of enamel thickness in the lower molars of red colobus (Procolobus badius) and Japanese macaque (Macaca fuscata).

The purpose of this study is to determine whether teeth are likely to retain their functional efficiency throughout an individual's life time. This was done by comparing the enamel volume, the cross-sectional enamel area and the pattern of enamel distribution on unworn M(2)s of folivorous (Procolobus badius: red colobus; n=8) and frugivorous (Macaca fuscata: Japanese macaque; n=6) cercopithecids. The enamel volume of M. fuscata is significantly greater than that of P. badius. As the lower molars of colobines become worn, the dentine is exposed on the buccal cusps and narrow enamel rims are formed around the dentine exposures. The buccal enamel rims are especially well-developed and sharp, a pattern that has probably been selected for as being advantageous for shredding fibrous plant materials. The results of this study demonstrate that the enamel on the lingual side of the protoconid, where dentine exposure occurs first, is much thinner in P. badius than it is in M. fuscata. In addition, the dentine is exposed and thin enamel rims are formed faster in P. badius than in M. fuscata. Also, P. badius has significantly thinner and more uniform enamel distribution on the buccal wall of the crown and a higher protoconid. The buccal flare is well-developed in M. fuscata, but poorly developed in P. badius. It is tentatively suggested that the undeveloped flare and thinner enamel of P. badius combine to enable this species to maintain narrow rims, even after dental attrition, while the high cusps may be an adaptation for providing narrow enamel rims throughout life.

Adaptation, Physiological↗